TRPV4 activation triggers the release of melatonin from human non-pigmented ciliary epithelial cells



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Alkozi, Hanan Awad and Pintor, Jesús (2015) TRPV4 activation triggers the release of melatonin from human non-pigmented ciliary epithelial cells. Experimental Eye Research, 136 . pp. 34-37. ISSN 0014-4835

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Melatonin is a neurohormone mainly produced in the pineal gland; nevertheless, various ocular structures such as the ciliary body, lens and the retina produce it. One of the roles of melatonin in the eye is the modulation of intraocular pressure, although little is known about the mechanisms that causes its presence in the aqueous humour. TRPV4 is a membrane channel which is activated by both physical and chemical stimuli. Therefore, this channel is sensitive to osmotic and hydrostatic pressure. As a consequence, TRPV4 results as an interesting candidate to study the relation between the activation of the TRPV4 channel and the production of melatonin. In this sense we have studied the role of the TRPV4 agonist GSK1016790A to modulate the production of melatonin in a cell line derived from human non-pigmented ciliary epithelial cells. The stimulation of the TRPV4 produced an increase in the extracellular melatonin levels changing from 8.5 ± 0.6 nM/well/30 min (control) to 23.3 ± 2.1 nM/well/30 min after 10 nM GSK1016790A application, this action being blocked by the selective antagonist RN 1734. The activation of the TRPV4 by GSK1016790A permitted to observe a melatonin increase which was concentration-dependent, and provided a pD2 value of −8.5 ± 0.1 (EC50 of 3.0 nM). In conclusion, the activation of the TRPV4 present in human non-pigmented ciliary epithelial cells can modulate the presence of extracellular melatonin, this being of relevance since this substance controls the dynamics of the aqueous humour.

Item Type:Article
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Received 11 December 2014; received in revised form 10 March 2015; accepted in revised form 27 April 2015; available online 29 April 2015.

Uncontrolled Keywords:Aqueous humour; GSK1016790A; Melatonin; RN 1734; TRPV4
Subjects:Medical sciences > Medicine > Biochemistry
Medical sciences > Medicine > Ophtalmology
Medical sciences > Optics > Eyes anatomy
ID Code:40617
Deposited On:20 Dec 2016 13:12
Last Modified:20 Dec 2016 13:14

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